MATERIALS AND METHODS: Febrile neutropenic patients treated between January 1996 and December 1997 at the pediatric oncology unit of University Hospital, Kuala Lumpur, were prospectively studied. Empirical antibiotic therapy consisted of ceftazidime and amikacin. Those who developed K. pneumoniae bacteremia were identified, and clinical features analyzed. Ceftazidime-resistance was documented via disk-diffusion testing. Production of extended-spectrum beta-lactamase (ESBL) was inferred on the basis of synergy between ceftazidime and amoxicillin-clavulanic acid. The different features between the two groups and variables associated with the development of CRKP bacteremia were analyzed using chi-square and t-tests and calculation of odds ratios. A multivariate analysis was used to identify independent factors for CRKP development.
RESULTS: Ceftazidime-resistance was seen in 51.6% of all K. pneumoniae isolates, and all these isolates were inferred to be ESBL producers. All isolates were sensitive to imipenem. Susceptibility to gentamicin was 90.5%. The mean continuous hospital stay prior to the detection of bacteremia was 13.7 days overall, but significantly longer in the CRKP group (21.9 d) compared to the CSKP group (4.3 d) (P = 0.003). Children with CRKP were more likely to have received antibiotics in the 2 weeks prior to detection of bacteremia (87.5% of cases) than the CSKP group (20.0% of cases) (P = 0.0008). Sepsis-related mortality was higher in those with CRKP (50.0%) than in the CSKP group (13.3%) (P = 0.02). Patients who did not receive CRKP-directed antibiotics within 48 hours of admission were more likely to have a fatal outcome than those who did (P = 0.009). Logistic regression analysis identified use of third-generation cephalosporins 2 weeks prior to presentation and a hospital stay of 2 weeks or more as independent risk factors for development of CRKP.
CONCLUSIONS: More than half of total K. pneumoniae isolated from blood cultures in the unit were ceftazidime-resistant. Children with febrile neutropenia with prolonged hospital stay and recent prior antibiotic exposure are at high risk of developing CRKP bacteremia. Mortality was significantly higher in this group. Early commencement of appropriate antibiotics (e.g., imipenem with or without gentamicin), according to susceptibility study results, may be beneficial in such circumstances.
METHODS: Two hundred and nine MRSA strains from year 2011 to 2012 were collected from a tertiary teaching hospital in Malaysia. The strains were characterized by antimicrobial susceptibility testing, staphylococcal cassette chromosome mec (SCCmec) typing, detection of Panton-Valentine leukocidin (PVL) gene, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Patient's demographic and clinical data were collected and correlated with molecular data by statistical analysis.
RESULTS: Male gender and patient >50 years of age (p
METHODS: A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC0-24) was estimated from a single trough level using established equations.
RESULTS: Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 μg mL-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 μg mL-1; P = 0.034). The mean ratio of estimated AUC0-24 and vancomycin MIC was 313.78 ± 117.17 μg h mL-1 in the non-responder group and 464.44 ± 139.06 μg h mL-1 in the responder group (P = 0.004). AUC0-24/MIC of ≥ 400 μg h mL-1 was documented for 77% of the responders and 27% of the non-responders (c2 = 7.03; P = 0.008).
CONCLUSIONS: Ratio of trough concentration/MIC and AUC0-24/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC0-24 alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.
METHODS: A retrospective observational study was performed on consecutive adult cases of ESBL and AmpC bacteremia at the Alfred Hospital from 2014 through April 2018.
RESULTS: Among 110 patients with ESBL (88.2%) and AmpC (14.5%) bacteremia episodes, 96.4% had comorbidities such as hematological malignancy (30%). Approximately 45% were on immunosuppressive drugs, while 69% had recent antibiotic exposure. Over 84% of bacteremias were hospital acquired or healthcare associated. Urinary tract was the main source of infection (40%) with E. coli being the commonest organism (66.4%). The isolates were least resistant to gentamicin (21.8%), which was often appropriately used in empirical therapy. About 34% of patients presented with severe sepsis or shock. The 30-day mortality rate was 20% with no correlation with inappropriate empirical antibiotics (52%). There was no significant mortality difference between carbapenem use in empirical and definitive therapy. Respiratory source [OR 11.77, 95% CI 1.30-106.85; p = 0.03], severe sepsis or shock [OR 5.17, 95% CI 1.37-19.55; p = 0.02] and inappropriate definitive therapy [OR 27.93, 95%CI 3.69-211.35; p = 0.001] were independent predictors for mortality.
CONCLUSION: The choice and appropriateness of empirical therapy were not associated with mortality in ESBL and AmpC bacteremia. Prudent use of carbapenem is reasonable with gentamicin as alternative. Emphasis should be on prompt resuscitation in severe sepsis and early detection of ESBL and AmpC to facilitate appropriate switch to definitive therapy.